Enhancing Fractionated Cancer Therapy: A Triple-Anthracene Photosensitizer Unleashes Long-Persistent Photodynamic and Luminous Efficacy.

Conventional photodynamic therapy (PDT) is often limited in treating solid tumors due to hypoxic conditions that impede the generation of reactive oxygen species (ROS), which are critical for therapeutic efficacy. To address this issue, a fractionated PDT protocol has been suggested, wherein light irradiation is administered in stages separated by dark intervals to permit oxygen recovery during these breaks. However, the current photosensitizers used in fractionated PDT are incapable of sustaining ROS production during the dark intervals, leading to suboptimal therapeutic outcomes (Table S1). To circumvent this drawback, we have synthesized a novel photosensitizer based on a triple-anthracene derivative that is designed for prolonged ROS generation, even after the cessation of light exposure. Our study reveals a unique photodynamic action of these derivatives, facilitating the direct and effective disruption of biomolecules and significantly improving the efficacy of fractionated PDT (Table S2). Moreover, the existing photosensitizers lack imaging capabilities for monitoring, which constraints the fine-tuning of irradiation parameters (Table S1). Our triple-anthracene derivative also serves as an afterglow imaging agent, emitting sustained luminescence postirradiation. This imaging function allows for the precise optimization of intervals between PDT sessions and aids in determining the timing for subsequent irradiation, thus enabling meticulous control over therapy parameters. Utilizing our novel triple-anthracene photosensitizer, we have formulated a fractionated PDT regimen that effectively eliminates orthotopic pancreatic tumors. This investigation highlights the promise of employing long-persistent photodynamic activity in advanced fractionated PDT approaches to overcome the current limitations of PDT in solid tumor treatment.

Lanthanide Inorganic Nanoparticles Enhance Semiconducting Polymer Nanoparticles Afterglow Luminescence for In Vivo Afterglow/Magnetic Resonance Imaging.

Dual/multimodal imaging strategies are increasingly recognized for their potential to provide comprehensive diagnostic insights in cancer imaging by harnessing complementary data. This study presents an innovative probe that capitalizes on the synergistic benefits of afterglow luminescence and magnetic resonance imaging (MRI), effectively eliminating autofluorescence interference and delivering a superior signal-to-noise ratio. Additionally, it facilitates deep tissue penetration and enables noninvasive imaging. Despite the advantages, only a limited number of probes have demonstrated the capability to simultaneously enhance afterglow luminescence and achieve high-resolution MRI and afterglow imaging. Herein, we introduce a cutting-edge imaging platform based on semiconducting polymer nanoparticles (PFODBT) integrated with NaYF4@NaGdF4 (Y@Gd@PFO-SPNs), which can directly amplify afterglow luminescence and generate MRI and afterglow signals in tumor tissues. The proposed mechanism involves lanthanide nanoparticles producing singlet oxygen (1O2) upon white light irradiation, which subsequently oxidizes PFODBT, thereby intensifying afterglow luminescence. This innovative platform paves the way for the development of high signal-to-background ratio imaging modalities, promising noninvasive diagnostics for cancer.

Chemical Design of Activatable Photoacoustic Probes for Precise Biomedical Applications.

Photoacoustic (PA) imaging technology, a three-dimensional hybrid imaging modality that integrates the advantage of optical and acoustic imaging, has great application prospects in molecular imaging due to its high imaging depth and resolution. To endow PA imaging with the ability for real-time molecular visualization and precise biomedical diagnosis, numerous activatable molecular PA probes which can specifically alter their PA intensities upon reacting with the targets or biological events of interest have been developed. This review highlights the recent developments of activatable PA probes for precise biomedical applications including molecular detection of the biotargets and imaging of the biological events. First, the generation mechanism of PA signals will be given, followed by a brief introduction to contrast agents used for PA probe design. Then we will particularly summarize the general design principles for the alteration of PA signals and activatable strategies for developing precise PA probes. Furthermore, we will give a detailed discussion of activatable PA probes in molecular detection and biomedical imaging applications in living systems. At last, the current challenges and outlooks of future PA probes will be discussed. We hope that this review will stimulate new ideas to explore the potentials of activatable PA probes for precise biomedical applications in the future.

Zinc-Carnosine Metallodrug Network as Dual Metabolism Inhibitor Overcoming Metabolic Reprogramming for Efficient Cancer Therapy.

The targeting of tumor metabolism as a novel strategy for cancer therapy has attracted tremendous attention. Herein, we develop a dual metabolism inhibitor, Zn-carnosine metallodrug network nanoparticles (Zn-Car MNs), which exhibits good Cu-depletion and Cu-responsive drug release, causing potent inhibition of both OXPHOS and glycolysis. Notably, Zn-Car MNs can decrease the activity of cytochrome c oxidase and the content of NAD+, so as to reduce ATP production in cancer cells. Thereby, energy deprivation, together with the depolarized mitochondrial membrane potential and increased oxidative stress, results in apoptosis of cancer cells. In result, Zn-Car MNs exerted more efficient metabolism-targeted therapy than the classic copper chelator, tetrathiomolybdate (TM), in both breast cancer (sensitive to copper depletion) and colon cancer (less sensitive to copper depletion) models. The efficacy and therapy of Zn-Car MNs suggest the possibility to overcome the drug resistance caused by metabolic reprogramming in tumors and has potential clinical relevance.

"Four-In-One" Design of a Hemicyanine-Based Modular Scaffold for High-Contrast Activatable Molecular Afterglow Imaging.

Afterglow luminescence (long persistent luminescence) holds great potential for nonbackground molecular imaging. However, current afterglow probes are mainly nanoparticles, and afterglow imaging systems based on organic small molecules are still lacking and have rarely been reported. Moreover, the lack of reactive sites and a universal molecular scaffold makes it difficult to design activatable afterglow probes. To address these issues, this study reports a novel kind of hemicyanine-based molecule scaffolds with stimuli-responsive afterglow luminescence, which is dependent on an intramolecular cascade photoreaction between 1O2 and the afterglow molecule to store the photoenergy for delayed luminescence after light cessation. As a proof of concept, three modular activatable molecular afterglow probes (MAPs) with a "four-in-one" molecular design by integrating a stimuli-responsive unit, 1O2-generating unit, 1O2-capturing unit, and luminescent unit into one probe are customized for quantification and imaging of targets including pH, superoxide anions, and aminopeptidase. Notably, MAPs show higher sensitivity in afterglow imaging than in fluorescence imaging because the responsive unit simultaneously controls the initiation of fluorescence (S1 to S0) and 1O2 generation (S1 to T1). Finally, MAPs are applied for high-contrast afterglow imaging of drug-induced hepatotoxicity, which is poorly evaluated in clinics and drug discovery. By reporting the sequential occurrence of oxidative stress and upregulation of aminopeptidase, such activatable afterglow probes allow noninvasive imaging of hepatotoxicity earlier than the serological and histology manifestation, indicating their promise for early diagnosis of hepatotoxicity.

Rational Design of a Double-Locked Photoacoustic Probe for Precise In Vivo Imaging of Cathepsin B in Atherosclerotic Plaques.

Atherosclerotic plaque rupture is a significant cause of acute cardiovascular events such as heart attack and stroke, triggered by the decomposition of fiber caps induced by cysteine cathepsin. However, the accurate measurement of cathepsin B (CTB) activity in plaques is challenging due to the low specificity and insufficient penetration depth of available atherosclerosis-associated cathepsin fluorescent probes, hampering reliable assessment of plaque vulnerability. To address these limitations, we added both lipophilic alkyl chain and hydrophilic CTB substrate to the hemicyanine scaffold to develop a lipid-unlocked CTB responsive probe (L-CRP) that uses lipids and CTB as two keys to unlock photoacoustic (PA) signals for measuring CTB activity in lipophilic environments. Such properties allow L-CRP for the reliable imaging of specific CTB activities in foam cells and atherosclerotic plaques while keeping in silence toward CTB in lipid-deficient environments, such as M1-type macrophages and LPS-induced inflammatory lesions. Moreover, the activatable PA signals of L-CRP exhibit a deeper tissue penetration ability (>1.0 cm) than current CTB probes based on near-infrared fluorescent imaging (∼0.3 cm), suitable for atherosclerosis imaging in living mice. In atherosclerotic mice, L-CRP dynamically reports intraplaque CTB levels, which is well-correlated with the plaque vulnerability characteristics such as fiber cap thickness, macrophage recruitment, and necrotic core size, thus enabling risk stratification of atherosclerotic mice complicated with pneumonia. Moreover, L-CRP successfully identifies atherosclerotic plaques in excised human artery tissues, promising for auxiliary diagnosis of plaque vulnerability in clinical application.

Noninvasive Imaging of Tumor Glycolysis and Chemotherapeutic Resistance via De Novo Design of Molecular Afterglow Scaffold.

Chemotherapeutic resistance poses a significant challenge in cancer treatment, resulting in the reduced efficacy of standard chemotherapeutic agents. Abnormal metabolism, particularly increased anaerobic glycolysis, has been identified as a major contributing factor to chemotherapeutic resistance. To address this issue, noninvasive imaging techniques capable of visualizing tumor glycolysis are crucial. However, the currently available methods (such as PET, MRI, and fluorescence) possess limitations in terms of sensitivity, safety, dynamic imaging capability, and autofluorescence. Here, we present the de novo design of a unique afterglow molecular scaffold based on hemicyanine and rhodamine dyes, which holds promise for low-background optical imaging. In contrast to previous designs, this scaffold exhibits responsive "OFF-ON" afterglow signals through spirocyclization, thus enabling simultaneous control of photodynamic effects and luminescence efficacy. This leads to a larger dynamic range, broader detection range, higher signal enhancement ratio, and higher sensitivity. Furthermore, the integration of multiple functionalities simplifies probe design, eliminates the need for spectral overlap, and enhances reliability. Moreover, we have expanded the applications of this afterglow molecular scaffold by developing various probes for different molecular targets. Notably, we developed a water-soluble pH-responsive afterglow nanoprobe for visualizing glycolysis in living mice. This nanoprobe monitors the effects of glycolytic inhibitors or oxidative phosphorylation inhibitors on tumor glycolysis, providing a valuable tool for evaluating the tumor cell sensitivity to these inhibitors. Therefore, the new afterglow molecular scaffold presents a promising approach for understanding tumor metabolism, monitoring chemotherapeutic resistance, and guiding precision medicine in the future.

Semiconducting Polymer Nanoparticles-Manganese Based Chemiluminescent Platform for Determining Total Antioxidant Capacity in Diabetic Mice.

The total antioxidant capacity (TAC) is a key indicator of the body's resistance to oxidative stress injury in diabetic patients. The measurement of TAC is important for effectively evaluating the redox state to prevent and control the occurrence of diabetes complications. However, there is a lack of a simple, convenient, and reliable method to detect the total antioxidant capacity in diabetes. Herein, we design a novel chemiluminescent platform based on semiconducting polymer nanoparticles-manganese (SPNs-MnVII) to detect the total antioxidant capacity of urine in diabetic mice. We synthesize semiconducting polymer nanoparticles with four different structures and discover the ability of MnVII to produce singlet oxygen (1O2) that is employed to excite thiophene-based SPNs (PFODBT) to emit near-infrared chemiluminescence. Notably, the chemiluminescent intensity has a good linear relationship with the concentration of MnVII (detection limit: 2.8 µM). Because antioxidants (e.g., glutathione or ascorbic acid) can react with MnVII, such a chemiluminescent tool of SPNs (PFODBT)-MnVII can detect the glutathione or ascorbic acid with a larger responsive range. Furthermore, the total antioxidant capacity of urine from mice is evaluated via SPNs (PFODBT)-MnVII, and there are statistically significant differences between diabetic and healthy mice. Thus, this new chemiluminescent platform of SPNs (PFODBT)-MnVII is convenient, efficient, and sensitive, which is promising for monitoring antioxidant therapy of diabetes.

Ionic-Wind-Enhanced Raman Spectroscopy without Enhancement Substrates.

Raman spectra are often masked by strong fluorescence, which severely hinders the applications of Raman spectroscopy. Herein, for the first time, we report ionic-wind-enhanced Raman spectroscopy (IWERS) incorporated with photobleaching (PB) as a noninvasive approach to detect fluorescent and vulnerable samples without a substrate. In this study, ionic wind (IW) generated by needle-net electrodes transfers charges to the sample surface in air on the scale of millimeters rather than nanometers in surface-enhanced Raman spectroscopy. Density functional theory calculations reveal that the ionic particles in IW increase the susceptibility of the sample molecules, thus enhancing the Raman signals. Meanwhile, the incorporation of IW with PB yields a synergistic effect to quench fluorescence. Therefore, this approach can improve the signal-to-noise ratio of Raman peaks up to three times higher than that with only PB. At the same time, IWERS can avoid sample pollution and destruction without substrates as well as high laser power. For archeological samples and a red rock as an analogue to Mars geological samples, IWERS successfully identified weak but key Raman peaks, which were masked by strong florescence. It suggests that IWERS is a promising tool for characterizations in the fields of archeology, planetary science, biomedicine, and soft matter.

Sensitive and quantitative in vivo analysis of PD-L1 using magnetic particle imaging and imaging-guided immunotherapy.

PURPOSE: The programmed cell death protein-1 (PD-1) and programmed cell death ligand-1 (PD-L1) expression correlate with the immunotherapeutic response rate. The sensitive and non-invasive imaging of immune checkpoint biomarkers is favorable for the accurate detection and characterization, image-guided immunotherapy in cancer precision medicine. Magnetic particle imaging (MPI), as a novel and emerging imaging modality, possesses the advantages of high sensitivity, no image depth limitation, positive contrast, and absence of radiation. Hence, in this study, we performed the pioneer investigation of monitoring PD-L1 expression using MPI and the MPI-guided immunotherapy. METHODS: We developed anti-PD-L1 antibody (aPDL1)-conjugated magnetic fluorescent hybrid nanoparticles (MFNPs-aPDL1) and utilized MPI in combination with fluorescence imaging (FMI) to dynamically monitor and quantify PD-L1 expression in various tumors with different PD-L1 expression levels. The ex vivo real-time polymerase chain reaction (qPCR), western blotting, and immunofluorescence staining analysis were further performed to validate the in vivo imaging observation. Moreover, the MPI was further performed for the guidance of immunotherapy. RESULTS: Our data showed that PD-L1 expression can be specifically and sensitively monitored and quantified using MPI and FMI imaging methods, which were validated by ex vivo qPCR and western blotting analysis. In addition, MPI-guided PD-L1 immunotherapy can enhance the effectiveness of cancer immunotherapy. CONCLUSION: To our best knowledge, this is the pioneer study to utilize MPI in combination with a newly developed MFNPs-aPDL1 imaging probe to dynamically visualize and quantify PD-L1 expression in tumor microenvironment. This imaging strategy may facilitate the clinical optimization of immunotherapy management.

Organic Afterglow Nanoparticles in Bioapplications.

Organic afterglow nanoparticles are unique optical materials that emit light long after cessation of excitation. Due to their advantages of no need for real-time light excitation, avoiding autofluorescence, low imaging background, high signal-to-background ratio, deep tissue penetration, and high sensitivity, afterglow imaging technology has been widely used in cell tracking, biosensing, cancer diagnosis, and cancer therapy, which provides an effective technical method for the acquisition of molecular information with high sensitivity, specificity and real-time at the cellular and living level. In this review, we summarize and illustrate the recent progress of organic afterglow imaging, focusing on the mechanism of organic afterglow materials and their biological application. Furthermore, we also discuss the potential challenges and the further directions of this field.

A novel ROS-Related chemiluminescent semiconducting polymer nanoplatform for acute pancreatitis early diagnosis and severity assessment.

Acute pancreatitis (AP) is a common and potentially life-threatening inflammatory disease of the pancreas. Reactive oxygen species (ROS) play a key role in the occurrence and development of AP. With increasing ROS levels, the degree of oxidative stress and the severity of AP increase. However, diagnosing AP still has many drawbacks, including difficulties with early diagnosis and undesirable sensitivity and accuracy. Herein, we synthesized a semiconducting polymer nanoplatform (SPN) that can emit ROS-correlated chemiluminescence (CL) signals. The CL intensity increased in solution after optimization of the SPN. The biosafety of the SPN was verified in vitro and in vivo. The mechanism and sensitivity of the SPN for AP early diagnosis and severity assessment were evaluated in three groups of mice using CL intensity, serum marker evaluations and hematoxylin and eosin staining assessments. The synthetic SPN can be sensitively combined with different concentrations of ROS to produce different degrees of high-intensity CL in vitro and in vivo. Notably, the SPN shows an excellent correlation between CL intensity and AP severity. This nanoplatform represents a superior method to assess the severity of AP accurately and sensitively according to ROS related chemiluminescence signals. This research overcomes the shortcomings of AP diagnosis in clinical practice and provides a novel method for the clinical diagnosis of pancreatitis in the future.

Ultrasmall PtMn nanoparticles as sensitive manganese release modulator for specificity cancer theranostics.

Manganese-based nanomaterials (Mn-nanomaterials) hold immense potential in cancer diagnosis and therapies. However, most Mn-nanomaterials are limited by the low sensitivity and low efficiency toward mild weak acidity (pH 6.4-6.8) of the tumor microenvironment, resulting in unsatisfactory therapeutic effect and poor magnetic resonance imaging (MRI) performance. This study introduces pH-ultrasensitive PtMn nanoparticles as a novel platform for enhanced ferroptosis-based cancer theranostics. The PtMn nanoparticles were synthesized with different diameters from 5.3 to 2.7 nm with size-dominant catalytic activity and magnetic relaxation, and modified with an acidity-responsive polymer to create pH-sensitive agents. Importantly, R-PtMn-1 (3 nm core) presents "turn-on" oxidase-like activity, affording a significant enhancement ratio (pH 6.0/pH 7.4) in catalytic activity (6.7 folds), compared with R-PtMn-2 (4.2 nm core, 3.7 folds) or R-PtMn-3 (5.3 nm core, 2.1 folds), respectively. Moreover, R-PtMn-1 exhibits dual-mode contrast in high-field MRI. R-PtMn-1 possesses a good enhancement ratio (pH 6.4/pH 7.4) that is 3 or 3.2 folds for T1- or T2-MRI, respectively, which is higher than that of R-PtMn-2 (1.4 or 1.5 folds) or R-PtMn-3 (1.1 or 1.2 folds). Moreover, their pH-ultrasensitivity enabled activation specifically within the tumor microenvironment, avoiding off-target toxicity in normal tissues during delivery. In vitro studies demonstrated elevated intracellular reactive oxygen species production, lipid peroxidation, mitochondrial membrane potential changes, malondialdehyde content, and glutathione depletion, leading to enhanced ferroptosis in cancer cells. Meanwhile, normal cells remained unaffected by the nanoparticles. Overall, the pH-ultrasensitive PtMn nanoparticles offer a promising strategy for accurate cancer diagnosis and ferroptosis-based therapy.

Degradable Magnetic Nanoplatform with Hydroxide Ions Triggered Photoacoustic, MR Imaging, and Photothermal Conversion for Precise Cancer Theranostic.

Theranostic agents based on inorganic nanomaterials are still suffered from the nonbiodegradable substances with long-term retention in body and unavoidable biological toxicity, as well as nonspecificity biodistribution with potential damage toward normal tissues. Here, we develop magnetic ions (FeIII, FeII, GdIII, MnII, and MnIII) coordinated nanoplatform (MICN) with framework structure and modify them with PEG (MICN-PEG). Notably, MICN-PEG demonstrates hydroxide ions (OH-) triggered the structure collapse along with responsive near-infrared photoacoustic (PA) signal, magnetic resonance imaging (MRI), and photothermal therapy (PTT) performances. Thereby, MICN-PEG is able to remain stable in tumors and exert excellent PA/MRI and PTT effects for multimodal imaging-guided cancer treatment. In contrast, MICN-PEG is gradually collapsed in normal tissues, resulting in the significant improvement of imaging accuracy and treatment specificity. MICN-PEG is gradually cleared after administration, minimizing concerns about the long-term toxicity.

Engineering of magnetic nanoparticles as magnetic particle imaging tracers.

Magnetic particle imaging (MPI) has recently emerged as a promising non-invasive imaging technique because of its signal linearly propotional to the tracer mass, ability to generate positive contrast, low tissue background, unlimited tissue penetration depth, and lack of ionizing radiation. The sensitivity and resolution of MPI are highly dependent on the properties of magnetic nanoparticles (MNPs), and extensive research efforts have been focused on the design and synthesis of tracers. This review examines parameters that dictate the performance of MNPs, including size, shape, composition, surface property, crystallinity, the surrounding environment, and aggregation state to provide guidance for engineering MPI tracers with better performance. Finally, we discuss applications of MPI imaging and its challenges and perspectives in clinical translation.

Ratiometric Semiconducting Polymer Nanoparticle for Reliable Photoacoustic Imaging of Pneumonia-Induced Vulnerable Atherosclerotic Plaque in Vivo.

Acute pneumonia can greatly increase the vulnerable risk of atherosclerotic plaque and contribute to the mortality of cardiovascular disease. To accurately assess the rupture risk caused by acute pneumonia, we developed a novel kind of ratiometric semiconducting polymer nanoparticle (RSPN) for photoacoustic imaging of vulnerable plaque in apolipoprotein E-deficient mice complicated with pneumonia. Specifically, RSPN can react with O2•- and exhibit the enhanced photoacoustic signals at about 690 nm, while 800 nm is regarded as an internal photoacoustic reference. As a result, RSPN can provide reliable determination of O2•- within aortic atherosclerosis by analyzing the ratios of photoacoustic signals, which can successfully reflect the oxidative stress level in vulnerable plaque. Therefore, RSPN enable to specifically distinguish plaque-bearing mice and plaque-bearing mice complicated with pneumonia from healthy mice, which provides a promising tool to predict the vulnerability of plaque for reducing the mortality of atherosclerotic-induced cardiovascular disease.

Overcoming Hypoxia-Induced Ferroptosis Resistance via a 19 F/1 H-MRI Traceable Core-Shell Nanostructure.

Lipid peroxides accumulation induced ferroptosis is an effective cell death pathway for cancer therapy. However, the hypoxic condition of tumor microenvironment significantly suppresses the efficacy of ferroptosis. Here, we design a novel nanoplatform to overcome hypoxia-induced ferroptosis resistance. Specifically, we synthesize a novel kind of perfluorocarbon (PFOB)@manganese oxide (MnOx) core-shell nanoparticles (PM-CS NPs). Owing to the good carrier of O2 as fuel, PM-CS NPs can induce higher level of ROS generation, lipid peroxidation and GSH depletion, as well as lower activity of GPX4, compared with MnOx NPs alone. Moreover, the supplement of O2 can relieve tumor hypoxia to break down the storage of intracellular lipid droplets and increase expression of ACSL4 (a symbol for ferroptosis sensitivity). Furthermore, upon stimulus of GSH or acidity, PM-CS NPs exhibit the "turn on" 19 F-MRI signal and activatable T1 /T2 -MRI contrast for correlating with the release of Mn. Finally, PM-CS NPs exert high cancer inhibition rate for ferroptosis based therapy via synergetic combination of O2 -mediated enhancement of key pathways of ferroptosis.

Ternary Alloy PtWMn as a Mn Nanoreservoir for High-Field MRI Monitoring and Highly Selective Ferroptosis Therapy.

Ferroptosis exhibits potential to damage drug-resistant cancer cells. However, it is still restricted with the "off-target" toxicity from the undesirable leakage of metal ions from ferroptosis agents, and the lack of reliable imaging for monitoring the ferroptosis process in living systems. Herein, we develop a novel ternary alloy PtWMn nanocube as a Mn reservoir, and further design a microenvironment-triggered nanoplatform that can accurately release Mn ions within the tumor to increase reactive oxygen species (ROS) generation, produce O2 and consume excess glutathione for synergistically enhancing nonferrous ferroptosis. Moreover, this nanoplatform exerts a responsive signal in high-field magnetic resonance imaging (MRI), which enables the real-time report of Mn release and the monitoring of ferroptosis initiation through the signal changes of T1 -/T2 -MRI. Thus, our nanoplatform provides a novel strategy to store, deliver and precisely release Mn ions for MRI-guided high-specificity ferroptosis therapy.

Tumor-Specific Multipath Nucleic Acid Damages Strategy by Symbiosed Nanozyme@Enzyme with Synergistic Self-Cyclic Catalysis.

The high proliferation efficiency, redox imbalance, and elevated nucleic acid repair capabilities of tumor cells severely restrict the theranostic efficacy. Selectively interference chaotic tumors with devastating nucleic acid damages (NUDs) properties are expected to overcome theranostic barriers. Here, an exquisite catalytic-based strategy with comprehensive NUDs mechanisms is demonstrated. In this regard, enzyme (glucose oxidase, GOD) symbioses nanozyme Cu3+x (PO4 )2 through biomineralization (abbreviated as Cu@GOD), GOD can disorder the metabolism by consuming glucose, thereby inhibiting the nutrition supply for nucleic acid repair. GOD-catalyzed H2 O2 guarantees the self-cyclic glutathione depletion and reactive oxygen species generation caused by Cu3+x (PO4 )2 , resulted the reduced antioxidation defense and enhanced oxidation assault, ensures an indiscriminate NUDs ability. Moreover, the high photothermal effect of Cu3+x (PO4 )2 induces effective tumor inhibition. Consequently, this substantial multipath NUDs strategy, with potentials of suppressing the cytoprotective mechanisms, amplifying the cellular oxidative stress, and disrupting the redox balance to ensure substantial irreversible NUDs, completely breaks the obstacle of chaotic tumors, providing new conceptual thinking for tumor proliferation inhibition.

Reactive Oxygen Correlated Chemiluminescent Imaging of a Semiconducting Polymer Nanoplatform for Monitoring Chemodynamic Therapy.

In chemodynamic therapy (CDT), real-time monitoring of reactive oxygen species (ROS) production is critical to reducing the nonspecific damage during CDT and feasibly evaluating the therapeutic response. However, CDT agents that can emit ROS-related signals are rare. Herein, we synthesize a semiconducting polymer nanoplatform (SPN) that can not only produce highly toxic ROS to kill cancer cells but also emit ROS-correlated chemiluminescent signals. Notably, the efficacy of both chemiluminescence and CDT can be significantly enhanced by hemin doping (∼10-fold enhancement for luminescent intensity). Such ROS-dependent chemiluminescence of SPN allows ROS generation within a tumor to be optically monitored during the CDT process. Importantly, SPN establishes an excellent correlation of chemiluminescence intensities with cancer inhibition rates in vitro and in vivo. Thus, our nanoplatform represents the first intelligent strategy that enables chemiluminescence-imaging-monitored CDT, which holds potential in assessing therapeutic responsivity and predicting treatment outcomes in early stages.